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Selective metal ion recognition using a fluorescent 1,8-diquinolylnaphthalene-derived sensor in aqueous solution
Tetrahedron 60 (2004) 11293–11297
Selective metal ion recognition using a fluorescent 1,8-diquinolylnaphthalene-derived sensor in aqueous solution Gilbert E. Tumambac, Charlene M. Rosencrance and Christian Wolf* Department of Chemistry, Georgetown University, 37th and O Streets, Washington, DC 20057 USA Received 9 March 2004; revised 24 June 2004; accepted 21 July 2004 Available online 24 August 2004
Abstract—The use of anti-1,8-bis(2,2 0 -diisopropyl-4,4 0 -diquinolyl)naphthalene, 1, for metal ion-selective fluorescence recognition has been investigated. Employing CuCl2, ZnCl2, FeCl2, and FeCl3 in fluorescence titration experiments of 1 revealed formation of a bluegreen light emitting bimetallic complex. A dramatic red-shift of the fluorescence maximum of 1 and metal ion-selective quenching was observed in the presence of Cu(II), Fe(II), and Fe(III)chlorides in acetonitrile. By contrast, addition of ZnCl2 was found to result in fluorescence enhancement, whereas Cu(I) did not induce any significant fluorescence change of 1. The sensor was found to undergo highly ion-selective fluorescence quenching in aqueous solution. Screening of main group and transition metal ions showed excellent selectivity for FeCl3 even in the presence of competing metal ions. q 2004 Elsevier Ltd. All rights reserved.
1. Introduction Because of the increasing demand in environmental and clinical sciences for fluorosensors that are capable of differentiating between metal ions and their oxidation states the development of sensor molecules for the detection of alkali, alkaline earth, and transition metals has recently received considerable attention.1 Based on our previous studies with selectively substituted 1,8-dipyridylnaphthalenes2 and 1,8-diacridylnaphthalenes,3 we assumed that incorporation of 2-isopropylquinolyl groups into the peripositions of naphthalene would afford a rigid and fluorescent bidentate ligand capable of selective metal ion recognition. Highly selective chemosensors for detection of Hg(II) and Zn(II) ions in aqueous solutions have recently been reported.4 Herein, we wish to describe the design and fluorescence behavior of anti-1,8-bis(2,2 0 -diisopropyl-4,4 0 diquinolyl)naphthalene, 1, a new chemosensor for highly selective recognition of Fe(III) in aqueous solution (Fig. 1).
congested 1 is the severe steric hindrance in the second cross-coupling reaction of intermediate 1-bromo-8-(2-isopropyl-4-quinolyl)naphthalene (Scheme 1). Screening of various catalysts including Pd(PPh 3) 4, PdCl 2(dppf), Pd2(dba)3/P(t-Bu)3, and [(t-Bu)2P(OH)]2PdCl2 and optimization of reaction conditions revealed that 1 can be formed by CuO-promoted5 Pd-catalyzed Stille cross-coupling in remarkable yields. Thus, cross-coupling of 2-isopropyl-4trimethylstannylquinoline, 2, and 1,8-dibromonaphthalene, 3, in the presence of 10 mol% of Pd(PPh3)4 and 2 equiv of CuO in DMF gave anti-1,8-bis(2,2 0 -diisopropyl-4,4 0 -diquinolyl)naphthalene, 1, in 36% yield after purification by chromatography and recrystallization from ethanol (Scheme 1). The space filling model of sensor 1 obtained by PM3 computations shows the unique structure of this highly congested bidentate ligand (Fig. 1). The antiparallel
2. Results and discussion The incorporation of two quinolyl rings into the peri positions of naphthalene requires two consecutive Stille or Suzuki cross-coupling steps of a 1,8-dihalonaphthalene and 2 equiv of a quinolyl-derived stannane or boronic acid, respectively. The major obstacle of the formation of highly Keywords: Stille coupling; Fluorosensor; Metal ion sensing. * Corresponding author. Tel.: C1-202-687-3468; fax: C1-202-687-6209; e-mail: [email protected] 0040–4020/$ - see front matter q 2004 Elsevier Ltd. All rights reserved. doi:10.1016/j.tet.2004.07.053
Figure 1. Structure and space filling model of 1,8-diquinolylnaphthalene 1. Hydrogens are omitted for clarity.
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in the presence of Cu(I) and Cu(II) thus provides a new venue for real-time detection of the oxidation state of copper salts.
Scheme 1. Reagents and conditions: 10 mol% Pd(PPh3)4, 4 equiv CuO, DMF, 100 8C, 13 h, ratio: 2/3Z3:1.
quinolyl moieties are almost perpendicular to the naphthalene ring. To minimize steric interactions, through-space Coulomb repulsion, and dipole–dipole interactions the two quinolyl groups are twisted and slightly splayed away from each other. The spatial arrangement of the 2-isopropylquinolyl rings thus creates a well-defined binding environment for metal ion-selective recognition. Our fluorescence studies revealed an emission maximum of 380 nm for the syn- and anti-isomers of 1 but different quantum yields. The quantum yield of syn-1 and anti-1 were determined as 2.0 and 11.6%, respectively. Because of its enhanced fluorescence we decided to employ anti-1 in metal ion sensing studies. The majority of fluorescent chemosensors reported to date exhibit a chelating group physically separated from a fluorophore by a spacer.6 However, smaller sensors such as anti-1 may afford superior cell permeability properties and are therefore particularly interesting with respect to biomedical applications. Fluorescence titrations using 1 and various transition metals were performed in acetonitrile at room temperature. We observed a striking change in the emission spectrum of the sensor in the presence of equimolar amounts of Cu(II), Fe(II), and Fe(III) chloride. Addition of these metal salts to a solution of anti-1 was found to result in the formation of a bluegreen light emitting complex with a red-shifted emission maximum of 520 nm. Increasing the metal ion concentration did not result in any further shift of the emission maximum. By contrast, the fluorescence spectrum of diquinolylnaphthalene 1 exhibiting a maximum at 380 nm did not change significantly upon addition of Cu(I) and Zn(II) (Fig. 2). The remarkable difference in the fluorescence maximum and intensity of the sensor molecule
In addition to the remarkable red-shift of the fluorescence maximum of anti-1 induced by CuCl2, FeCl2, and FeCl3, at approximately equimolar concentrations and by ZnCl2 when employed in high excess, we observed metal ionselective quenching and enhancing effects. Fluorescence titration experiments showed that CuCl does not significantly enhance the fluorescence signal at 520 nm even at high excess, whereas addition of CuCl2, ZnCl2, FeCl2, and FeCl3 gave non-linear Stern–Vo¨lmer plots. Titration with FeCl2 and FeCl3 resulted in strong fluorescence at 520 nm, which reached a maximum at a metal ion-sensor ratio of approximately 4:1 and 3:1, respectively. A further increase in metal ion excess was found to decrease the fluorescence intensity and ultimately caused quenching indicating coexistence of different complex species in solution (Fig. 3). Fluorescence titration experiments using CuCl2 revealed formation of a 2:1 complex, which corresponds to a mol fraction of Cu(II) of 0.67 (Fig. 4). Because of the geometry of the diquinolylnaphthalene framework exhibiting cofacial hetaryl rings, the sensor affords two remote quinolyl nitrogens with a lone electron pair available for metal ion coordination in the hetaryl plane (Fig. 1). Apparently, both quinolyl nitrogens can undergo metal ion coordination, which results in the formation of a Cu(II)2–1 complex. Interestingly, Zn(II) remains a strong enhancer of the fluorescence signal at 520 nm at high concentration, whereas Cu(II), Fe(II), and Fe(III) induce fluorescence quenching at high metal ion/sensor ratios (Fig. 5). Notably, very effective quenching was observed at high Fe(III)sensor ratio (Fig. 6). The sigmoidal quenching curve observed at high Fe(III)/anti-1 ratio indicates that different quenching mechanisms and cooperative metal ion recognition might be operative.7 The selective fluorescence response of sensor 1 opens a new venue for real-time analysis of transition metal ions. The different fluorescence response of the sensor to Cu(I) and Cu(II) allows differentiation of the oxidation states of
Figure 2. Fluorescence of anti-1 in the presence of Cu(I), Cu(II), Zn(II), Fe(II), and Fe(III) in acetonitrile. The concentration of anti-1 was 4.3!10K5 M and the metal ion concentration was 1.0!10K4 M. Excitation wavelength: 320 nm.
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Figure 3. Fluorescence enhancement of anti-1 induced by FeCl2 and FeCl3. The concentration of anti-1 was 4.3!10K5 M. Excitation wavelength: 320 nm, emission wavelength: 520 nm.
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Figure 7. Stern–Vo¨lmer plot of anti-1 in the presence of CuCl and CuCl2 (ratio metal ion/anti-1O10). The concentration of anti-1 was 4.3!10K5M. Excitation wavelength: 320 nm, emission wavelength: 520 nm.
copper (Fig. 7). The fluorescence quenching observed with CuCl2, FeCl2, and FeCl3 at high excess is probably a result of photo-induced electron transfer. Because this quenching mechanism is not available for d10-metal complexes, Cu(I) and Zn(II) do not provide additional relaxation pathways for excited anti-2 and are therefore inefficient quenchers. Fluorescent enhancement induced by binding to Zn(II) or other transition metals has been attributed to enhanced conformational restriction upon metal complexation.8
Figure 4. Fluorescence titration of anti-1 using Cu(II). The concentration of anti-1 was 4.3!10K5 M. Excitation wavelength: 320 nm, emission wavelength: 520 nm.
Figure 5. Stern–Vo¨lmer plot of anti-1 in the presence of ZnCl2. The concentration of anti-1 was 4.3!10K5 M. Excitation wavelength: 320 nm, emission wavelength: 520 nm.
Figure 6. Stern–Vo¨lmer plot of anti-1 in the presence of FeCl2 and FeCl3 (ratio metal ion/anti-1O10). The concentration of anti-1 was 4.3!10K5 M. Excitation wavelength: 320 nm, emission wavelength: 520 nm.
We then employed sensor 1 in water/acetonitrile to assess its use in aqueous solutions. The fluorescence spectrum of 1 in the presence of metal ions was found to afford maxima at 390 and 520 nm in a 1:1 water/acetontrile (v/v) solution (Fig. 8). Screening of a broad variety of main group and transition metal chlorides revealed efficient fluorescence quenching by FeCl3. It is noteworthy that ferric and ferrous chloride reduce the fluorescence maximum at 520 nm, whereas Na(I), K(I), Ca(II), Cr(II), Mn(II), Co(II), Ni(II), Cu(I), Cu(II), Zn(II), Cd(II), and Hg(II) do not show any significant quenching. The quenching effects on the fluorescence maximum at 390 nm is even more dramatic. We observed that addition of Fe(III) to an aqueous solution of 1 decreases the emission intensity to less than 2%. The fluorescence intensity at 390 nm decreased to approximately 30% in the presence of Cr(II) and Fe(II), whereas other metal ions do not show any significant effects (Fig. 9). Moreover, excellent selectivity for Fe(III) was found in the presence of Cr(II), Mn(II), Cu(I), and Zn(II). The highly selective quenching of 1,8-diquinolylnaphthalene 1 by ferric and ferrous chloride in aqueous solutions may be utilized for the diagnosis of various iron-related diseases. The determination of iron levels in blood serum and other body fluids is indispensable for the study and treatment of nutritional and metabolic diseases that result in low or high iron levels. Iron metabolism disorders have been reported to cause iron-deficiency anemia and hemochromatosis which might ultimately cause liver cancer, liver cirrhosis, arthritis, diabetes or heart failure.9 Recent studies have linked lateonset neurodegenerative disorders such as Parkinson’s disease to elevated iron levels.10 The monitoring iron levels in blood serum and cell extracts has become an integral part of the diagnosis and treatment of cancer because tumor cells require iron to grow and proliferate. Iron also plays a crucial role in important infectious diseases such as malaria.11
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Figure 8. Fluorescence spectrum of 1 in the absence and presence of various metal ions in water/acetonitrile (1:1). The concentration of anti-1 was 4.3!10K5M. Metal ion concentration: 10K3 M. Excitation wavelength: 320 nm.
insensitive to the presence of Cr(II), Mn(II), Cu(I), and Zn(II). 4. Experimental 4.1. General All commercially available reagents and solvents were used without further purification. Sensor 1 was purified by flash chromatography on SiO2 (particle size 0.032–0.063 mm). NMR spectra were obtained at 300 MHz (1H NMR) and 75 MHz (13C NMR) using CDCl3 as the solvent. Chemical shifts are reported in ppm relative to TMS. Fluorescence experiments were conducted using degassed solutions and a Fluoromax-2 spectrometer from Instruments S.A. Inc. The quantum yield of each isomer of 1 was determined in acetonitrile following a procedure described by Jones and co-workers.12 The diquinoline isomers were excited at 320 nm and relative integrated intensities of the emission spectra were compared to naphthalene which has a quantum yield of 0.2 in acetonitrile. Figure 9. Fluorescence intensity of 1 in water/acetonitrile. The concentration of anti-1 was 4.3!10K5 M. Metal ion concentration: 10K3 M. Excitation wavelength: 320 nm, emission wavelength: 390 nm.
3. Conclusion 1,8-Diquinolylnaphthalene 1 was found to exhibit a complex fluorescence behavior in the presence of transition metals. A significant red-shift of the fluorescence maximum of 1 was observed upon addition of approximately equimolar amounts of Cu(II), Fe(II), and Fe(III) in acetonitrile and attributed to the formation of a bimetallic complex. Quenching and non-linear Stern–Vo¨lmer plots indicating co-existence of different metal complexes of 1 were observed at high excess of these metal ions. By contrast, CuCl did not induce quenching or a red-shift of the fluorescence maximum of 1 and ZnCl2 was found to enhance the red-shifted emission maximum at high concentration. The highly Fe(III)-selective quenching of the fluorescence maxima in aqueous solution makes 1 an attractive sensor for trace analysis and diagnosis of ironrelated diseases. The Fe(III)-selective quenching was
4.1.1. Preparation of anti-1,8-bis(2,2 0 -diisopropyl-4,4 0 diquinolyl)naphthalene, 1. To a solution of 1,8-dibromonaphthalene, 3, (0.3 g, 1.0 mmol), Pd(PPh3)4 (130 mg, 10 mol%) and CuO (0.30 g, 4.0 mmol) in 10 mL of anhydrous DMF was added 2-isopropyl-4-trimethylstannylquinoline, 2, (1.0 g, 3.0 mmol) in 5 mL of DMF. The reaction was stirred at 100 8C for 13 h, cooled to room temperature, quenched with aqueous NH4OH, and extracted with diethyl ether. The combined organic layers were washed with H2O, dried over MgSO4 and concentrated under vacuum. Purification by flash chromatography (hexanes/EtOAc/Et3NZ100:20:1) and crystallization from ethanol gave 1 (168 mg, 0.36 mmol, 36%) as white crystals. dH (CDCl3) 0.80 (d, JZ6.9 Hz, 6H), 0.98 (d, JZ6.9 Hz, 6H), 2.34 (sept, JZ6.9 Hz, 2H), 6.34 (s, 2H), 7.18 (dd, JZ 1.1, 8.2 Hz, 2H), 7.23–7.29 (m, 4H), 7.54 (ddd, JZ1.4, 6.7, 8.4 Hz, 2H), 7.62 (dd, JZ7.1, 8.2 Hz, 2H), 7.87 (d, JZ 8.5 Hz, 2H), 8.13 (dd, JZ1.4, 8.4 Hz, 2H). dC (CDCl3) 21.4, 21.5, 36.4, 120.2, 120.4, 125.6, 125.7, 126.9, 128.7, 129.7, 129.9, 130.7, 131.5, 134.7, 136.1, 147.1, 148.2, 165.8. EI/MS: m/z 466 (100%, MC), 451 (94, MCK Me), 436 (5, MCK2Me), 423 (23, MCKi-Pr), 253 (5,
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MC-isopropylquinolyl). LC/APCI/MS: m/z 467 [100%, (MCH)C]. Anal. Calcd for C34H30N2: C, 86.70; H, 7.68; N, 5.62. Found: C, 86.27; H, 7.23; N, 5.87.
Acknowledgements C.W. gratefully acknowledges the National Science Foundation for a CAREER award (CHE 0347368).
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References and notes 1. (a) Unob, F.; Asfari, Z.; Vicens, J. Tetrahedron Lett. 1998, 39, 2951–2954. (b) Purrello, R.; Gurrieri, S.; Lauceri, R. Coord. Chem. Rev. 1999, 192, 683–706. (c) Leray, I.; Valeur, B.; O’Reilly, F.; Jiwan, J.-L. H.; Soumillion, J.-P.; Valeur, B. Chem. Commun. 1999, 795–796. (d) Valeur, B.; Leray, I. Coord. Chem. Rev. 2000, 205, 3–40. (e) de Silva, A. P.; Fox, D. B.; Huxley, A. J. M.; Moody, T. S. Coord. Chem. Rev. 2000, 205, 41–57. (f) Deo, S.; Godwin, H. A. J. Am. Chem. Soc. 2000, 122, 174–175. (g) Singh, A.; Yao, Q.; Tong, L.; Still, C. W.; Sames, D. Tetrahedron Lett. 2000, 41, 9601–9605. (h) Prodi, L.; Montalti, M.; Zaccheroni, N.; Dallavalle, F.; Folesani, G.; Lanfranchi, M.; Corradini, R.; Pagliari, S.; Marchelli, R. Helv. Chim. Acta 2001, 84, 690–706. (i) Burdette, S. C.; Walkup, G. K.; Spingler, B.; Tsien, R. Y.; Lippard, S. J. Am. Chem. Soc. 2001, 123, 7831–7841. (j) Baxter, P. N. W. Chem. Eur. J. 2002, 5250–5264. (k) Chao, C.-T.; Huang, W.-P. J. Am. Chem. Soc. 2002, 124, 6246–6247. (l) Yang, N. C.; Jeong, J. K.; Suh, D. H. Chem. Lett. 2003, 32, 40–41. (m) Grabchev, I.; Chovelon, J.-M.; Qian, X. New J. Chem. 2003, 27, 337–340. (n) Zheng, Y.; Gattas-Asfura, K. M.; Li, C.; Andreopoulos, F. M.; Pham, S. M.; Leblanc, R. M. J. Phys. Chem. B 2003, 107, 483–488. (o) Kim, J. S.; Noh, K. H.; Lee, S. H.; Kim, S. K.; Yoon, J. J. Org. Chem. 2003, 68, 597–600. (p) Clark,
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Selective metal ion recognition using a fluorescent 1,8-diquinolylnaphthalene-derived sensor in aqueous solution Gilbert E. Tumambac, Charlene M. Rosencrance and Christian Wolf* Department of Chemistry, Georgetown University, 37th and O Streets, Washington, DC 20057 USA Received 9 March 2004; revised 24 June 2004; accepted 21 July 2004 Available online 24 August 2004
Abstract—The use of anti-1,8-bis(2,2 0 -diisopropyl-4,4 0 -diquinolyl)naphthalene, 1, for metal ion-selective fluorescence recognition has been investigated. Employing CuCl2, ZnCl2, FeCl2, and FeCl3 in fluorescence titration experiments of 1 revealed formation of a bluegreen light emitting bimetallic complex. A dramatic red-shift of the fluorescence maximum of 1 and metal ion-selective quenching was observed in the presence of Cu(II), Fe(II), and Fe(III)chlorides in acetonitrile. By contrast, addition of ZnCl2 was found to result in fluorescence enhancement, whereas Cu(I) did not induce any significant fluorescence change of 1. The sensor was found to undergo highly ion-selective fluorescence quenching in aqueous solution. Screening of main group and transition metal ions showed excellent selectivity for FeCl3 even in the presence of competing metal ions. q 2004 Elsevier Ltd. All rights reserved.
1. Introduction Because of the increasing demand in environmental and clinical sciences for fluorosensors that are capable of differentiating between metal ions and their oxidation states the development of sensor molecules for the detection of alkali, alkaline earth, and transition metals has recently received considerable attention.1 Based on our previous studies with selectively substituted 1,8-dipyridylnaphthalenes2 and 1,8-diacridylnaphthalenes,3 we assumed that incorporation of 2-isopropylquinolyl groups into the peripositions of naphthalene would afford a rigid and fluorescent bidentate ligand capable of selective metal ion recognition. Highly selective chemosensors for detection of Hg(II) and Zn(II) ions in aqueous solutions have recently been reported.4 Herein, we wish to describe the design and fluorescence behavior of anti-1,8-bis(2,2 0 -diisopropyl-4,4 0 diquinolyl)naphthalene, 1, a new chemosensor for highly selective recognition of Fe(III) in aqueous solution (Fig. 1).
congested 1 is the severe steric hindrance in the second cross-coupling reaction of intermediate 1-bromo-8-(2-isopropyl-4-quinolyl)naphthalene (Scheme 1). Screening of various catalysts including Pd(PPh 3) 4, PdCl 2(dppf), Pd2(dba)3/P(t-Bu)3, and [(t-Bu)2P(OH)]2PdCl2 and optimization of reaction conditions revealed that 1 can be formed by CuO-promoted5 Pd-catalyzed Stille cross-coupling in remarkable yields. Thus, cross-coupling of 2-isopropyl-4trimethylstannylquinoline, 2, and 1,8-dibromonaphthalene, 3, in the presence of 10 mol% of Pd(PPh3)4 and 2 equiv of CuO in DMF gave anti-1,8-bis(2,2 0 -diisopropyl-4,4 0 -diquinolyl)naphthalene, 1, in 36% yield after purification by chromatography and recrystallization from ethanol (Scheme 1). The space filling model of sensor 1 obtained by PM3 computations shows the unique structure of this highly congested bidentate ligand (Fig. 1). The antiparallel
2. Results and discussion The incorporation of two quinolyl rings into the peri positions of naphthalene requires two consecutive Stille or Suzuki cross-coupling steps of a 1,8-dihalonaphthalene and 2 equiv of a quinolyl-derived stannane or boronic acid, respectively. The major obstacle of the formation of highly Keywords: Stille coupling; Fluorosensor; Metal ion sensing. * Corresponding author. Tel.: C1-202-687-3468; fax: C1-202-687-6209; e-mail: [email protected] 0040–4020/$ - see front matter q 2004 Elsevier Ltd. All rights reserved. doi:10.1016/j.tet.2004.07.053
Figure 1. Structure and space filling model of 1,8-diquinolylnaphthalene 1. Hydrogens are omitted for clarity.
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in the presence of Cu(I) and Cu(II) thus provides a new venue for real-time detection of the oxidation state of copper salts.
Scheme 1. Reagents and conditions: 10 mol% Pd(PPh3)4, 4 equiv CuO, DMF, 100 8C, 13 h, ratio: 2/3Z3:1.
quinolyl moieties are almost perpendicular to the naphthalene ring. To minimize steric interactions, through-space Coulomb repulsion, and dipole–dipole interactions the two quinolyl groups are twisted and slightly splayed away from each other. The spatial arrangement of the 2-isopropylquinolyl rings thus creates a well-defined binding environment for metal ion-selective recognition. Our fluorescence studies revealed an emission maximum of 380 nm for the syn- and anti-isomers of 1 but different quantum yields. The quantum yield of syn-1 and anti-1 were determined as 2.0 and 11.6%, respectively. Because of its enhanced fluorescence we decided to employ anti-1 in metal ion sensing studies. The majority of fluorescent chemosensors reported to date exhibit a chelating group physically separated from a fluorophore by a spacer.6 However, smaller sensors such as anti-1 may afford superior cell permeability properties and are therefore particularly interesting with respect to biomedical applications. Fluorescence titrations using 1 and various transition metals were performed in acetonitrile at room temperature. We observed a striking change in the emission spectrum of the sensor in the presence of equimolar amounts of Cu(II), Fe(II), and Fe(III) chloride. Addition of these metal salts to a solution of anti-1 was found to result in the formation of a bluegreen light emitting complex with a red-shifted emission maximum of 520 nm. Increasing the metal ion concentration did not result in any further shift of the emission maximum. By contrast, the fluorescence spectrum of diquinolylnaphthalene 1 exhibiting a maximum at 380 nm did not change significantly upon addition of Cu(I) and Zn(II) (Fig. 2). The remarkable difference in the fluorescence maximum and intensity of the sensor molecule
In addition to the remarkable red-shift of the fluorescence maximum of anti-1 induced by CuCl2, FeCl2, and FeCl3, at approximately equimolar concentrations and by ZnCl2 when employed in high excess, we observed metal ionselective quenching and enhancing effects. Fluorescence titration experiments showed that CuCl does not significantly enhance the fluorescence signal at 520 nm even at high excess, whereas addition of CuCl2, ZnCl2, FeCl2, and FeCl3 gave non-linear Stern–Vo¨lmer plots. Titration with FeCl2 and FeCl3 resulted in strong fluorescence at 520 nm, which reached a maximum at a metal ion-sensor ratio of approximately 4:1 and 3:1, respectively. A further increase in metal ion excess was found to decrease the fluorescence intensity and ultimately caused quenching indicating coexistence of different complex species in solution (Fig. 3). Fluorescence titration experiments using CuCl2 revealed formation of a 2:1 complex, which corresponds to a mol fraction of Cu(II) of 0.67 (Fig. 4). Because of the geometry of the diquinolylnaphthalene framework exhibiting cofacial hetaryl rings, the sensor affords two remote quinolyl nitrogens with a lone electron pair available for metal ion coordination in the hetaryl plane (Fig. 1). Apparently, both quinolyl nitrogens can undergo metal ion coordination, which results in the formation of a Cu(II)2–1 complex. Interestingly, Zn(II) remains a strong enhancer of the fluorescence signal at 520 nm at high concentration, whereas Cu(II), Fe(II), and Fe(III) induce fluorescence quenching at high metal ion/sensor ratios (Fig. 5). Notably, very effective quenching was observed at high Fe(III)sensor ratio (Fig. 6). The sigmoidal quenching curve observed at high Fe(III)/anti-1 ratio indicates that different quenching mechanisms and cooperative metal ion recognition might be operative.7 The selective fluorescence response of sensor 1 opens a new venue for real-time analysis of transition metal ions. The different fluorescence response of the sensor to Cu(I) and Cu(II) allows differentiation of the oxidation states of
Figure 2. Fluorescence of anti-1 in the presence of Cu(I), Cu(II), Zn(II), Fe(II), and Fe(III) in acetonitrile. The concentration of anti-1 was 4.3!10K5 M and the metal ion concentration was 1.0!10K4 M. Excitation wavelength: 320 nm.
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Figure 3. Fluorescence enhancement of anti-1 induced by FeCl2 and FeCl3. The concentration of anti-1 was 4.3!10K5 M. Excitation wavelength: 320 nm, emission wavelength: 520 nm.
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Figure 7. Stern–Vo¨lmer plot of anti-1 in the presence of CuCl and CuCl2 (ratio metal ion/anti-1O10). The concentration of anti-1 was 4.3!10K5M. Excitation wavelength: 320 nm, emission wavelength: 520 nm.
copper (Fig. 7). The fluorescence quenching observed with CuCl2, FeCl2, and FeCl3 at high excess is probably a result of photo-induced electron transfer. Because this quenching mechanism is not available for d10-metal complexes, Cu(I) and Zn(II) do not provide additional relaxation pathways for excited anti-2 and are therefore inefficient quenchers. Fluorescent enhancement induced by binding to Zn(II) or other transition metals has been attributed to enhanced conformational restriction upon metal complexation.8
Figure 4. Fluorescence titration of anti-1 using Cu(II). The concentration of anti-1 was 4.3!10K5 M. Excitation wavelength: 320 nm, emission wavelength: 520 nm.
Figure 5. Stern–Vo¨lmer plot of anti-1 in the presence of ZnCl2. The concentration of anti-1 was 4.3!10K5 M. Excitation wavelength: 320 nm, emission wavelength: 520 nm.
Figure 6. Stern–Vo¨lmer plot of anti-1 in the presence of FeCl2 and FeCl3 (ratio metal ion/anti-1O10). The concentration of anti-1 was 4.3!10K5 M. Excitation wavelength: 320 nm, emission wavelength: 520 nm.
We then employed sensor 1 in water/acetonitrile to assess its use in aqueous solutions. The fluorescence spectrum of 1 in the presence of metal ions was found to afford maxima at 390 and 520 nm in a 1:1 water/acetontrile (v/v) solution (Fig. 8). Screening of a broad variety of main group and transition metal chlorides revealed efficient fluorescence quenching by FeCl3. It is noteworthy that ferric and ferrous chloride reduce the fluorescence maximum at 520 nm, whereas Na(I), K(I), Ca(II), Cr(II), Mn(II), Co(II), Ni(II), Cu(I), Cu(II), Zn(II), Cd(II), and Hg(II) do not show any significant quenching. The quenching effects on the fluorescence maximum at 390 nm is even more dramatic. We observed that addition of Fe(III) to an aqueous solution of 1 decreases the emission intensity to less than 2%. The fluorescence intensity at 390 nm decreased to approximately 30% in the presence of Cr(II) and Fe(II), whereas other metal ions do not show any significant effects (Fig. 9). Moreover, excellent selectivity for Fe(III) was found in the presence of Cr(II), Mn(II), Cu(I), and Zn(II). The highly selective quenching of 1,8-diquinolylnaphthalene 1 by ferric and ferrous chloride in aqueous solutions may be utilized for the diagnosis of various iron-related diseases. The determination of iron levels in blood serum and other body fluids is indispensable for the study and treatment of nutritional and metabolic diseases that result in low or high iron levels. Iron metabolism disorders have been reported to cause iron-deficiency anemia and hemochromatosis which might ultimately cause liver cancer, liver cirrhosis, arthritis, diabetes or heart failure.9 Recent studies have linked lateonset neurodegenerative disorders such as Parkinson’s disease to elevated iron levels.10 The monitoring iron levels in blood serum and cell extracts has become an integral part of the diagnosis and treatment of cancer because tumor cells require iron to grow and proliferate. Iron also plays a crucial role in important infectious diseases such as malaria.11
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Figure 8. Fluorescence spectrum of 1 in the absence and presence of various metal ions in water/acetonitrile (1:1). The concentration of anti-1 was 4.3!10K5M. Metal ion concentration: 10K3 M. Excitation wavelength: 320 nm.
insensitive to the presence of Cr(II), Mn(II), Cu(I), and Zn(II). 4. Experimental 4.1. General All commercially available reagents and solvents were used without further purification. Sensor 1 was purified by flash chromatography on SiO2 (particle size 0.032–0.063 mm). NMR spectra were obtained at 300 MHz (1H NMR) and 75 MHz (13C NMR) using CDCl3 as the solvent. Chemical shifts are reported in ppm relative to TMS. Fluorescence experiments were conducted using degassed solutions and a Fluoromax-2 spectrometer from Instruments S.A. Inc. The quantum yield of each isomer of 1 was determined in acetonitrile following a procedure described by Jones and co-workers.12 The diquinoline isomers were excited at 320 nm and relative integrated intensities of the emission spectra were compared to naphthalene which has a quantum yield of 0.2 in acetonitrile. Figure 9. Fluorescence intensity of 1 in water/acetonitrile. The concentration of anti-1 was 4.3!10K5 M. Metal ion concentration: 10K3 M. Excitation wavelength: 320 nm, emission wavelength: 390 nm.
3. Conclusion 1,8-Diquinolylnaphthalene 1 was found to exhibit a complex fluorescence behavior in the presence of transition metals. A significant red-shift of the fluorescence maximum of 1 was observed upon addition of approximately equimolar amounts of Cu(II), Fe(II), and Fe(III) in acetonitrile and attributed to the formation of a bimetallic complex. Quenching and non-linear Stern–Vo¨lmer plots indicating co-existence of different metal complexes of 1 were observed at high excess of these metal ions. By contrast, CuCl did not induce quenching or a red-shift of the fluorescence maximum of 1 and ZnCl2 was found to enhance the red-shifted emission maximum at high concentration. The highly Fe(III)-selective quenching of the fluorescence maxima in aqueous solution makes 1 an attractive sensor for trace analysis and diagnosis of ironrelated diseases. The Fe(III)-selective quenching was
4.1.1. Preparation of anti-1,8-bis(2,2 0 -diisopropyl-4,4 0 diquinolyl)naphthalene, 1. To a solution of 1,8-dibromonaphthalene, 3, (0.3 g, 1.0 mmol), Pd(PPh3)4 (130 mg, 10 mol%) and CuO (0.30 g, 4.0 mmol) in 10 mL of anhydrous DMF was added 2-isopropyl-4-trimethylstannylquinoline, 2, (1.0 g, 3.0 mmol) in 5 mL of DMF. The reaction was stirred at 100 8C for 13 h, cooled to room temperature, quenched with aqueous NH4OH, and extracted with diethyl ether. The combined organic layers were washed with H2O, dried over MgSO4 and concentrated under vacuum. Purification by flash chromatography (hexanes/EtOAc/Et3NZ100:20:1) and crystallization from ethanol gave 1 (168 mg, 0.36 mmol, 36%) as white crystals. dH (CDCl3) 0.80 (d, JZ6.9 Hz, 6H), 0.98 (d, JZ6.9 Hz, 6H), 2.34 (sept, JZ6.9 Hz, 2H), 6.34 (s, 2H), 7.18 (dd, JZ 1.1, 8.2 Hz, 2H), 7.23–7.29 (m, 4H), 7.54 (ddd, JZ1.4, 6.7, 8.4 Hz, 2H), 7.62 (dd, JZ7.1, 8.2 Hz, 2H), 7.87 (d, JZ 8.5 Hz, 2H), 8.13 (dd, JZ1.4, 8.4 Hz, 2H). dC (CDCl3) 21.4, 21.5, 36.4, 120.2, 120.4, 125.6, 125.7, 126.9, 128.7, 129.7, 129.9, 130.7, 131.5, 134.7, 136.1, 147.1, 148.2, 165.8. EI/MS: m/z 466 (100%, MC), 451 (94, MCK Me), 436 (5, MCK2Me), 423 (23, MCKi-Pr), 253 (5,
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MC-isopropylquinolyl). LC/APCI/MS: m/z 467 [100%, (MCH)C]. Anal. Calcd for C34H30N2: C, 86.70; H, 7.68; N, 5.62. Found: C, 86.27; H, 7.23; N, 5.87.
Acknowledgements C.W. gratefully acknowledges the National Science Foundation for a CAREER award (CHE 0347368).
2.
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